Interferon-gamma is a T cell-derived cytokine that exhibits anti-viral and immunomodulatory effects on many cell types. Recombinant human interferon-gamma is approved for the treatment of chronic granulomatous disease and severe malignant osteopetrosis. Other indications currently being investigated inhuman clinical trials include idiopathic pulmonary fibrosis, liver fibrosis, hepatitis C and ovarian cancer. [unreadable] Interferon-gamma has a short half-life after subcutaneous administration (25-35 min) that necessitates frequent administration and reduces potential efficacy. We propose to create polymer modified interferon-gamma-proteins that can be administered less frequently, but with greater potency, than existing interferon-gamma products. During Phase I we will identify sites in interferon-gamma that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified interferon-gamma proteins for testing in animal disease models. The improved characteristics of the novel interferon-gamma proteins should reduce the amount of interferon gamma required per patient, enhance efficacy, reduce toxicity, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Interferon-gamma is a member of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoietic disorders [unreadable] [unreadable]